title: Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma.
abstract: OBJECTIVE
  Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment.
  
  
  METHODS
  Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2) , days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m(2) and prednisone 60mg/m(2) , days 1-4, cycles 1-9; N=344) or MP alone (N=338).
  
  
  RESULTS
  Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P=0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P≤0.0001) and CR/PR (P≤0.01). Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 (P=0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease.
  
  
  CONCLUSIONS
  These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma.
authors.affiliation: Myeloma Study Group, Belgian Hematological Society, Belgium. michel.delforge@uzleuven.be
authors.forename: Michel
authors.initials: M
authors.lastname: Delforge
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Nuriet K
authors.initials: NK
authors.lastname: Khuageva
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.forename: Maria T
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Olga S
authors.initials: OS
authors.lastname: Samoilova
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Hila
authors.initials: H
authors.lastname: Magen-Nativ
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Ricci
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: William
authors.initials: W
authors.lastname: Deraedt
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001847:Bone Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016723:Bone Remodeling / Q000187:drug effects*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant
chemical_list: D015415:Biomarkers; D001897:Boronic Acids; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011719:Pyrazines; D000069286:Bortezomib; D000469:Alkaline Phosphatase; D008558:Melphalan; D011241:Prednisone